The long-term goal of application EY04859 is the investigation of the genetic and microenvironmental factors that regulate the survival and differentiation of retinal neurons and photoreceptors. The studies are based on a multidisciplinary approach that involves: i) analysis of genetic influences by gene transfer into retinal cells in vivo and in vitro, ii) experimental manipulation of the cellular microenvironment in ovo and in culture, and iii) characterization of the phenotypic properties expressed by differentiating retinal cells using in situ hybridization, immunocytochemistry, autoradiography, single cell cDNA synthesis, RTPCR, real time PCR, Northern blots and image analysis. Aspects of the dynamics and regulation of photoreceptor cell differentiation that will be studied include: i) the developmental relationships between retinal progenitors that develop as rods or cones, ii) the coordinated expression of visual pigments and other photoreceptor specific-molecules during differentiation, iii) the development of outer segments, and iv) the effects on these phenomena of CNTF and the activin and BMP families of growth factors. The role of the homeobox genes Pax-6 and Chx-1O in the differentiation of retinal neurons and photoreceptors will also be investigated. The information derived from these studies is expected to further our understanding of the mechanisms of retinal development, and may also be relevant for some therapeutic approaches to retinal degenerations.